Absence of correlation between skewed X inactivation in blood and serum creatine-kinase levels in Duchenne/Becker female carriers

The pattern of X inactivation in lymphocyte DNA was investigated in 107 Duc henne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) carriers (102 asymptomatic and 5 manifesting carriers) and 117 normal female contro ls of different ages, with the aim: a) to analyze the pattern of X inactiva tion in blood DNA of a large number of DMD/BMD carriers as compared to norm al female controls; b) to determine if there is a decrease in serum creatin e kinase (CK) levels with age in obligate DMD/BMD carriers; c) to determine if there is a correlation between X-chromosome inactivation and serum CK a mong asymptomatic DMD/BMD carriers of different ages or with different clin ical manifestations in symptomatic carriers. A high proportion of females s howed extremely skewed X inactivation (>90% of one X preferentially inactiv ated), which was almost the same among carriers and normal controls (19 and 24%, respectively), The mean serum CK was significantly greater among youn g (<20 years old) than adult (>20 years old) DMD/BMD carriers and it decrea sed significantly until age 20 with an apparent stabilization afterwards. N o statistically significant correlation was found between the proportion of active X-DMD in blood and serum CK activity in DMD/BMD carriers although i t was higher among those less than 20 years old. Our observations suggest t hat highly skewed X-chromosome pattern in blood (with preferential inactiva tion of the X-N chromosome) is not enough to predict that a young DMD carri er will develop muscular weakness, Am. J. Med. Genet. 80: 356-361, 1998. (C ) 1998 Wiley-Liss, Inc.